Summary

The purpose of this research study is to determine whether we can purify and grow a
population of cells from the participants blood (iNKT cells) and then safely give them back
to the participant in increased numbers, and whether these cells will then stimulate the
bodies own immune response against the cancer. These iNKT cells have been used in
laboratory studies and information from these and other research studies suggest that
increasing the number of these cells in the blood can stimulate the immune response against
tumors.

Study Design

Primary Outcomes

To determine the feasibility of isolating and expanding in vitro autologous iNKT cells from cancer patients for therapeutic use.

time frame:
2 years

To assess the safety of treatment with in vitro expanded autologous iNKT cells alone, and in conjunction with GM-CSF.

time frame:
2 years

Secondary Outcomes

Measure

To assess the biological activity of reinfused in vitro expanded autologous iNKT cells.

time frame:
2 years

To assess the biological activity of reinfused in vitro expanded autologous iNKT cells in conjunction with GM-CSF.

time frame:
2 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria:
- Stage IV melanoma
- ECOG Performance Status 0-1
- Estimated life expectancy of 6 months or greater
- 18 years of age or older
- Adequate renal, hepatic and hematological function as outlined in protocol
- Adequate pulmonary and cardiac function as outlined in protocol
- Prior therapies must be discontinued at least 4 weeks prior to the leukopheresis to
obtain iNKT cells. This does not include palliative surgery or radiation therapy,
which may be used prior to leukopheresis or during the interval between leukopheresis
and iNKT cell reinfusion
- Melanoma patients must not have brain metastases based on a negative MRI obtained
within 4 weeks prior to screening, and must not have a history of brain metastases
- No other significant medical, surgical or psychiatric condition that, in the judgment
of the PI, would interfere with compliance to the protocol regimen
Exclusion Criteria:
- Pregnant or nursing women
- Active systemic infection, positive HIV, HBV, or HCV serology, or immune deficiency
disease
- Autoimmune disease that currently requires systemic therapy with immunosuppressive
agents
- Known hypersensitivity to GM-CSF or DMSO
- Other active malignancy other than squamous cell or basal cell of the skin

Additional Information

Official title

A Phase I Trial of in Vitro Expanded Autologous Invariant Natural Killer Cells in Cancer

Principal investigator

Steven Balk, MD, PhD

Description

- The first step in the study will be to collect iNKT cells from the participants
peripheral blood. For this procedure an intravenous catheter will be used to remove
the blood. The white blood cells will be removed from the blood and the red blood
cells and plasma will be returned to the participant (leukopheresis).
- We will then purify the iNKT cells from these collected white blood cells, and will
grow them in culture plates in the lab under strictly controlled sterile conditions.
This can take 4-6 weeks.
- If we are successful in growing the iNKT cells to large enough numbers, they will be
divided into 3 equal doses. Participants will receive one dose of these cells by
intravenous infusion every 2 weeks or days 1, 15 and 29. A blood sample will be taken
immediately before each infusion, and at 1 and 4 hours after each infusion.
Participants will be asked to return for blood samples on day 2, 3, 4 and 8 after
infusion.
- The initial group of 3-6 participants will not receive any other therapy with the iNKT
cell infusions. However, the subsequent group of 6 patients will in addition receive
GM-CSF, which can further stimulate the immune system and may increase the effects of
the iNKT cells. This medication is administered by subcutaneous injection and will be
given daily for 10 days beginning the day of the second and third infusion.
- Participants will be on this research study for about 14 weeks, which includes the time
for the cell purification and culture, treatment, and follow-up observation.

Trial information was received from ClinicalTrials.gov and was last updated in February 2012.